Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/102809
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Type: Journal article
Title: Characterization of a hepatitis C virus-like particle vaccine produced in a human hepatocyte-derived cell line
Author: Earnest-Silveira, L.
Chua, B.
Chin, R.
Christiansen, D.
Johnson, D.
Herrmann, S.
Ralph, S.
Vercauteren, K.
Mesalam, A.
Meuleman, P.
Das, S.
Boo, I.
Drummer, H.
Bock, C.
Gowans, E.
Jackson, D.
Torresi, J.
Citation: Journal of General Virology, 2016; 97(8):1865-1876
Publisher: Microbiology Society
Issue Date: 2016
ISSN: 0022-1317
1465-2099
Statement of
Responsibility: 
L. Earnest-Silveira, B. Chua, R. Chin, D. Christiansen, D. Johnson, S. Herrmann, S. A. Ralph, K. Vercauteren, A. Mesalam, P. Meuleman, S. Das, I. Boo, H. Drummer, C.-T. Bock, E. J. Gowans, D. C. Jackson and Joseph Torresi
Abstract: An effective immune response against hepatitis C virus (HCV) requires the early development of multi-specific class 1 CD8+ and class II CD4+ T-cells together with broad neutralizing antibody responses. We have produced mammalian-cell-derived HCV virus-like particles (VLPs) incorporating core, E1 and E2 of HCV genotype 1a to produce such immune responses. Here we describe the biochemical and morphological characterization of the HCV VLPs and study HCV core-specific T-cell responses to the particles. The E1 and E2 glycoproteins in HCV VLPs formed non-covalent heterodimers and together with core protein assembled into VLPs with a buoyant density of 1.22 to 1.28 g cm⁻³. The HCV VLPs could be immunoprecipited with anti-ApoE and anti-ApoC. On electron microscopy, the VLPs had a heterogeneous morphology and ranged in size from 40 to 80 nm. The HCV VLPs demonstrated dose-dependent binding to murine-derived dendritic cells and the entry of HCV VLPs into Huh7 cells was blocked by anti-CD81 antibody. Vaccination of BALB/c mice with HCV VLPs purified from iodixanol gradients resulted in the production of neutralizing antibody responses while vaccination of humanized MHC class I transgenic mice resulted in the prodution of HCV core-specific CD8+ T-cell responses. Furthermore, IgG purified from the sera of patients chronically infected with HCV genotypes 1a and 3a blocked the binding and entry of the HCV VLPs into Huh7 cells. These results show that our mammalian-cell-derived HCV VLPs induce humoral and HCV-specific CD8+ T-cell responses and will have important implications for the development of a preventative vaccine for HCV.
Keywords: virus-like particles; Hepatitis C; neutralizing antibody
Rights: © 2016 The Authors
RMID: 0030047306
DOI: 10.1099/jgv.0.000493
Grant ID: http://purl.org/au-research/grants/nhmrc/1060436
http://purl.org/au-research/grants/nhmrc/1060433
http://purl.org/au-research/grants/nhmrc/543139
http://purl.org/au-research/grants/nhmrc/1062504
Appears in Collections:Medicine publications

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